Fluoro beta-carboline compounds

Abstract

In one aspect, the invention provides compounds of Formula I, and salts, hydrates and isomers thereof. In another aspect, the invention provides a method of promoting bone formation in a subject in need thereof by administering to the subject a therapeutically effective amount of a compound of Formula I. The present invention also provides orthopedic and periodontal devices, as well as methods for the treatment of renal disease, diabetes, bone loss, and cancer, using a compound of Formula I.

Description

CROSS-REFERENCES TO RELATED APPLICATIONS[0001]This application claims the benefit of priority under 35 U.S.C § 119(e) to U.S. Provisional Application Ser. No. 62 / 718,604 filed Aug. 14, 2018, the disclosure of which is incorporated herein by reference in its entirety.STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT[0002]NOT APPLICABLEREFERENCE TO A “SEQUENCE LISTING,” A TABLE, OR A COMPUTER PROGRAM LISTING APPENDIX SUBMITTED ON A COMPACT DISK[0003]NOT APPLICABLEBACKGROUND OF THE INVENTION[0004]Bone homeostasis involves the counterbalancing processes of bone formation and bone resorption. Increased bone resorption and loss of bone homeostasis is associated with a number of diseases and disorders, such as osteoporosis and Paget's disease. All FDA approved therapeutics for treating low bone density, except Teriparatide, do so by stopping bone resorption, hence antiresoptives. Antiresorptives act on the osteoclast cell by stopping them from res...

AI Technical Summary

Benefits of technology

[0021]In a second embodiment, the present invention provides a method of promoting bone formation and fusion in a subject in need thereof. The method includes administering to the subject a therapeutically effective amount of a compound of Formula I as described herein, thereby promoting bone formation in the subject. Bone formation can be systemic or local. For local bone formation, in some embodiments, the compound may be administered with an osteoconductive agent, e.g., an osteoconductive matrix.

[0022]In a third embodiment, the present invention provides a method of treating renal damage. The method includes administering to a subject in need thereof, a therapeutically effective amount of a compound of Formula I.

[0023]In a fourth embodiment, the present invention provides a method of treating diabetes. The method includes administering to a subject in need thereof, a therapeutically effective amount of a compound of Formula I.

[0024]In a fifth embodiment, the present invention provides a method of treating cancer. The method includes administering to a subject in need thereof, a therapeutically effective amount of a compound of Formula I.

Problems solved by technology

However, the use of BMP agonists for treating systemic disease has not been pursued past an FDA Phase I Clinical Trial.

However, demineralized bone matrix is generally sourced from donor cadaver banks and carries certain risks such as disease transmission or bacterial contamination.

The use of demineralized bone or similar osteoconductive material, which is known in the art, has not resulted in the desired effects fusing long bones.

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